The research proposed has two related general goals: to increase our understanding of the primary molecular mechanisms of action of glucocorticoids, with focus on the actions on rat thymus cells and other cells of the immune system; to elucidate the consequences of these actions at the cellular and tissue level, with particular emphasis on the physiology and pharmacology of immunosuppression and antiinflammatory effects. We will investigate (1) the kinetics and molecular mechanism of glucocorticoid-receptor complex activation in intact thymus cells, using column chromatography to separate non-activated, activated and other forms of these complexes; (2) the biochemical mechanism and cellular consequences of the rapid glucose-dependent inhibitory effect we have recently discovered of glucocorticoids on lipid synthesis in thymus cells; (3) the time-course and cellular distribution of changes that we have found in preliminary experiments and produced by glucocorticoids in methionine incorporation into cytosol proteins of thymus cells; (4) the mechanism, identity of target cells, and possible physiological implications for the whole organism of glucocorticoid inhibition of T-cell growth factor production by antigen-and mitogen-simulated cells in culture; (5) the mechanism, presence in normal cells, and possible consequences for immune and inflammatory reactions of the inhibition of Fc receptor expression by glucocorticoids that we have demonstrated recently with HL-60 cells in culture; (6) the validity of current methods for determining inhibitory effects of glucocorticoids on prostaglandin production by various cells, and the extent to which production of prostaglandins other than those investigated so far is inhibited; (7) the thermodynamic parameters of transfer of various steroids from water to a nonpolar medium, in order to assess relative contributions of different polar and nonpolar regions of steroids to interactions likely to be encountered in steroid-receptor complexes.